3-Pyridineacetic acid → Risedronate

HRID 658289

Reaction equation

HRID 658289 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([OH:10])=O)[CH:2]=1.[P:11]([OH:14])([OH:13])[OH:12].P(Cl)(Cl)Cl>ClC1C=CC=CC=1>[CH:5]1[CH:6]=[N:1][CH:2]=[C:3]([CH2:7][C:8]([P:11]([OH:14])([OH:13])=[O:12])([P:11]([OH:14])([OH:13])=[O:12])[OH:10])[CH:4]=1

Participants

5

Reactant 3

HCID 1083-Pyridineacetic acidHCID 24387Phosphorus trichlorideHCID 107909Phosphorous acid

Product 1

HCID 5245RisedronateYield 58.1%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
87.5 °C

Procedure

3-Pyridine acetic acid (25 g) in 500 ml of chlorobenzene added to phosphorous acid (35.5 g). The reaction mixture was heated up to 85-90° C. To the reaction mixture phosphorous trichloride (58.97 g) was added slowly to obtain a yellowish rigid, thick mass. The reaction mass was cooled to ambient temperature. The solvent was decanted. Demineralized water (200 ml) was added to the reaction mass and refluxed azeotropically, to remove residual chlorobenzene. Filtered through hyflo bed while hot, washed with hot demineralized water. The reaction mass was cooled to 0-5° C., stirred for 1.0 hour, filtered the solid and washed to get risedronic acid (30.0 g, yield 58%) having purity of 83.98% by HPLC.

Workup

  1. customto obtain a yellowish rigid, thick mass
  2. temperatureThe reaction mass was cooled to ambient temperature
  3. customThe solvent was decanted
  4. additionDemineralized water (200 ml) was added to the reaction mass
  5. temperaturerefluxed azeotropically
  6. customto remove residual chlorobenzene
  7. filtrationFiltered through hyflo bed while hot,
  8. washwashed with hot demineralized water
  9. temperatureThe reaction mass was cooled to 0-5° C.
  10. filtrationfiltered the solid
  11. washwashed

Sources & evidence

ORD record
ord-591d8d365cca484e912361e5db6945b7
Source dataset
uspto-grants-2011_12
Patent number
US08076483B2

Linked notes

Loading…